What is the maximum recommended dose of midodrine for treating orthostatic hypotension?

Maximum Dose of Midodrine for Orthostatic Hypotension

The maximum recommended dose of midodrine for treating orthostatic hypotension is 10 mg three times daily, with a total daily dose not exceeding 30 mg. 1

Dosing Guidelines

• Standard dosing regimen:

  • 10 mg three times daily
  • Doses should be given during daytime hours when upright position is needed
  • Recommended dosing intervals: approximately 4 hours apart
  • Typical schedule: morning (upon arising), midday, and late afternoon (not later than 6 PM)

• Dose titration:

  • Starting dose may be lower (2.5-5 mg three times daily)
  • May increase gradually based on response and tolerability
  • Can be given at 3-hour intervals if required for symptom control, but not more frequently

• Maximum doses:

  • Single doses as high as 20 mg have been given to patients
  • However, severe and persistent supine hypertension occurs at a high rate (approximately 45%) at the 20 mg dose 1
  • Total daily doses greater than 30 mg have been tolerated by some patients, but safety and efficacy have not been systematically established 1

Administration Considerations

• Midodrine should not be given:

  • After the evening meal
  • Less than 4 hours before bedtime
  • This timing restriction helps reduce the risk of supine hypertension during sleep 1

• For patients with renal impairment:

  • Initiate treatment using 2.5 mg doses
  • Use caution as desglymidodrine (active metabolite) is excreted renally 1

Efficacy and Monitoring

• Midodrine increases standing systolic blood pressure by approximately 15-30 mmHg at 1 hour after a 10 mg dose 1, 2

  • Effects typically persist for 2-3 hours
  • The 10 mg dose has been shown to increase standing systolic pressure by about 22 mmHg (28%) 2

• Regular monitoring is essential:

  • Supine and standing blood pressure should be monitored regularly
  • Discontinue midodrine if supine blood pressure increases excessively 1
  • Treatment should only be continued in patients who demonstrate symptomatic improvement

Common Side Effects

• Supine hypertension (8% of patients)
• Scalp pruritus/tingling (13.5% of patients)
• Urinary urgency (4% of patients)
• Piloerection (goosebumps)
• Headache and nervousness

Special Considerations

• In the context of hepatorenal syndrome, midodrine has been used in combination with octreotide and albumin, with midodrine titrated up to a maximum of 12.5 mg orally three times per day 3
• Midodrine is removed by dialysis, which may be relevant for patients undergoing hemodialysis 1

While some studies have investigated higher doses (up to 20 mg), the significant increase in supine hypertension risk at these doses makes the standard maximum of 10 mg three times daily (30 mg total daily dose) the recommended upper limit for most patients.